Chondrocytes have been known to play important roles in the life of vertebrates, such as skeleton formation by endochondral ossification or smoothing of movements by articular cartilage. Damages in articular cartilages formed by chondrocytes are believed to be an important factor accelerating the progress of diseases such as osteoarthritis. Despite of the important in vivo roles of chondrocytes, the regulatory mechanism of differentiation from undifferentiated mesenchymal cells into chondrocytes has not been revealed at all.
On the other hand, adipocytes derived from undifferentiated mesenchymal cells like chondrocytes have been known to play an important role in the control of in vivo energy supply by accumulating lipid droplets in cytoplasms. It is needless to say that excessive accumulation of fats in adipocytes causes obesity and is taken as a hazardous factor for many diseases of adults. It is reported that the differentiation mechanism of adipocytes is controlled by an intranuclear receptor PPAR-γ2 for a physiological ligand prostaglandin J2, a transcription factor C/EBP-α or the like, but the mechanism has not been fully revealed.
As used herein, the undifferentiated mesenchymal cells generally mean those having a plurality of differentiation potencies, particularly mesoderm-derived cells having pluripotency. Specifically, mouse embryo-derived C3H10T1/2 (Cell, 17;771-779, 1979), rat fetus-derived RCJ3.1 (J. Cell. Bio., 106:2139-2151, 1988), rat neonate-derived ROB (Calcif. Tissue Int. 49 (3): 221-225, 1991) or the like have been known.
Cell lines having differentiation potency into chondrocytes and adipocytes seem to be useful for studying the regulatory mechanism of differentiation from such undifferentiated mesenchymal cells into chondrocytes and adipocytes, and include known cell lines derived from embryos (Cell, 17, 771 (1979)), tumors (J. Cell Biol. 130, 1461 (1995)), neonatal animals (J. Cell Biol. 106, 2139 (1988)) or the like, but any those derived normal adult animals have not been known at present.
If a clonal cell line of undifferentiated mesenchymal cells capable of differentiating into chondrocytes and adipocytes were established from a normal adult animal such as a normal adult mouse, it would provide a very useful means for studying the regulatory mechanism of differentiation of these cells in adult individuals.